S-adenosylhomocysteine hydrolase plays a critical role in regulating AdoMet-dependent methylations in eukaryotic cells by regulating the ratio of AdoMet/AdoHcy. Several approaches are being used to determine the structure and function of this enzyme. 1) Structure Determination: The enzyme has been purified to homogeneity from rat liver. Conformational changes for active and inactive forms of the enzyme have been examined by fluorescence, circular dichroism, and by photoaffinity labeling of the active sites. Peptide fragments of the protein have been isolated and partial amino acid sequences determined. Oligonucleotide probes from the peptide sequences and antibodies are being used to screen a cDNA library from rat liver to obtain the nucleic acid sequence. 2) Ligand Binding and Kinetic Properties: The role of NAD, nucleotide, and cAMP binding in regulating the catalytic activity has been studied. A large number of adenosine and adenosylhomocysteine analogs have been examined for their ability to function as inhibitors and/or substrates of the enzyme. 3) Biological Effects of Inhibitors: In vitro these adenosine analogs can form very potent and specific inhibitors of transmethylation reactions, and these inhibitors have a wide range of biological activities, including antiviral activity against several RNA and DNA viruses, inhibition of leukocyte chemotaxis, and stimulation of cell differentiation.